Carbapenem-resistant Acinetobacter baumannii healthcare-associated infections: antimicrobial resistance and its spread as a global threat
Authors: Muralidharan Manjusha, Madhavan Yasasve, Muthupandian Saravanan, Melaku A. Belete
Journal: International Journal of Surgery (2023)

Carbapenems are a class of antibiotics that are effective against a wide variety of bacteria because of their distinctive structure, which consists of a carbapenem coupled to β-lactam ring that provides resistance to most lactamases, including metallo-lactamase (MBL) and extended-spectrum-lactamases. Furthermore, carbapenems are among the most effective medications used to treat bacterial infections1. Acinetobacter baumannii is now recognized as a significant threat to many facilities worldwide. Its enormous capacity to acquire or upregulate antibiotic drug resistance determinants has deservedly catapulted it to the forefront of scientific interest .Infections caused by A. baumannii are a common source of complications for patients in the ICU2. A. baumannii healthcare-associated infections (HAIs) have been linked to an elevated risk of mortality ranging from 8 to 40%. A. baumannii's exceptional capacity to gain resistance to several antibiotics, together with the pathogen's remarkable ability to survive for an extended period of time, are causes for serious concern. Although A. baumannii is most commonly found in ICUs, it has lately been linked to a wide variety of infectious diseases in military troops and organ transplantation3,4. As of late, it has come to light that A. baumannii possesses outer membrane proteins (OMPs) that contribute to its carbapenem resistance. Clinical isolates of A. baumannii lacked detectable carbapenemase activity, and this resistance to imipenem was linked to the loss of a 29 kDa OMP. It has been shown that the loss of a heat-modifiable 29 kDa OMP, dubbed CarO (an A. baumannii OMP involved in carbapenem resistance), is linked to resistance to imipenem and meropenem in multidrug-resistant A. baumannii clinical isolates. Cloning and characterization of the chromosomal region encoding CarO in clinical isolates revealed that the A. baumannii genome contains just a single copy of CarO, which is organized into a single transcriptional unit. The polypeptide encoded by the CarO gene consists of 247 amino acid residues and has a canonical N-terminal signal sequence as well as a predicted transmembrane barrel structure. CarO was disrupted by unique insertion elements in carbapenem-resistant clinical isolates of A. baumannii, lending credence to the idea that CarO plays a role in the uptake of carbapenem drugs by A. baumannii5. Studies highlight another obstacle that bacteria's mobile elements present to efforts to curb the spread of antibiotic resistance. Only the OprD of Pseudomonas aeruginosa, another nonfermentative pathogen belonging to the family Pseudomonadaceae of the class Proteobacteria, has been characterized to date as a specialized OM channel for carbapenems6. OprD is involved in the uptake of specific peptides and basic amino acids, and mutations that render OprD nonfunctional are a common cause of carbapenem resistance in clinical P. aeruginosa strains. But A. baumannii CarO is significantly smaller and has no conserved primary sequence homology to P. aeruginosa OprD. Furthermore, immunoblot analysis of the OMP fractions of various A. baumannii strains using an antiserum directed against P. aeruginosa OprD and the absence of OprD homologs in the recently released genome of Acinetobacter spp. strain ADP1 suggest that OMPs whose sequences are related to OprD are seemingly absent in Acinetobacter spp. (GenBank accession number CR543861)7. As a result, CarO may behave as an OprD analog in A. baumannii, allowing the pathogen to take up carbapenems. The physiological roles of this protein in A. baumannii are being investigated, as is the possibility that CarO achieves its function via forming complexes with other OMPs8. Finally, the hypothesized mechanism of carbapenem resistance may be limited in its general diffusion because CarO homolog genes appear to be limited to a specific family of the class Proteobacteria, the Moraxellaceae. In fact, many members of this family are recognized or suspected carcinogens The unsettling likelihood that they could eventually evolve carbapenem resistance via a similar mechanism calls for more awareness and research4. In conclusion, the emergence and spread of antibiotic resistance can be halted through the following steps: reasoned utilization antibiotics in all configurations; execution of infection control measures in hospital environments; creation of strategies to reduce the risks of exposure; advancement of rapid diagnostic tests; initiatives of research on antibacterial resistance preventative measures and surveillance; and advancement of research on novel antibiotics (Fig. 1). Concerningly, A. baumannii tends to grow in clonal fashion within institutions or cities, making its worldwide epidemiology a cause for alarm. There is undeniably a need for novel medicines, and as doctors, microbiologists, and scientists, we must take a holistic approach to the creation of effective new antimicrobial drugs. To convince the public and policymakers of the medical and economic benefits of addressing the danger of antimicrobial resistance, a worldwide and coordinated approach is required.Figure 1: Proper interventions in carbapenem-resistant Acinetobacter baumannii control.Ethical Approval and the relevant judgment's reference number Not applicable. Data statement All data are available in the manuscript. Sources of funding No source of funding. Research registration unique identifying number (UIN) Name of the registry: not applicable. Unique identifying number or registration ID: not applicable. Hyperlink to your specific registration (must be publicly accessible and will be checked): not applicable. Author contribution M.Y.: investigation, writing – original draft preparation. M.M.: data collection, visualization, writing – original draft preparation. M.S.: conceptualization, writing – reviewing and editing and supervision. M.A.B.: conceptualization, writing – reviewing and editing and supervision. Guarantor Melaku Ashagrie Belete. Conflicts of interest Authors declare that they have no conflicts of interest.